The entourage effect

The entourage effect is a proposal. Palmitoylethanolamide and anandamide share a breakdown enzyme, FAAH. If palmitoylethanolamide occupies that enzyme, anandamide might last longer and act more strongly.

The evidence

• In cells, palmitoylethanolamide made anandamide more potent at the TRPV1 receptor. The concentration of anandamide needed for a half-maximal response fell from 0.44 to 0.22 micromolar.

The evidence against

• Rankin and Fowler 2020 report that in humans and in dogs, oral palmitoylethanolamide did not produce a significant change in plasma anandamide levels.

On that basis, the review does not treat the entourage effect as an established mechanism for palmitoylethanolamide taken by mouth.